Without limiting the scope of the invention, its background is described in connection with cytokine-induced response, pro-inflammatory treatments, methods and compositions to maintain viability and reduce inflammation and apoptosis of transplanted islet cells.
Islet cell transplantation (ICTx) has emerged as a promising alternative therapy for “brittle” Type I diabetes mellitus (T1DM) in recent years and involves isolating the islets from deceased donor pancreas and transplanting them into T1DM patient liver. Successful transplantation can improve glycemic control, relieve the patient from insulin dependence and improve quality of life. However, clinical outcome is not always good due to significant loss of islet mass during or after transplantation. The loss of islets is caused by several reasons including instant blood-mediated inflammatory reaction (IBMIR) and adaptive immune response. There is incremental evidence that cytokines play a crucial role in both processes. Cytokines themselves can directly trigger islet cell death.
U.S. Pat. No. 7,695,718 issued to Scolinger et al. (2010) discloses methods for the treatment and/or prevention of Type 2 diabetes, insulin resistance and disease states and conditions characterized by insulin resistance, obesity, hyperglycemia, hyperinsulinemia and Type 1 diabetes, comprising administering to a subject an effective amount of anti-IL-1 beta antibody or fragment thereof.
U.S. Patent Publication No. 20090093434 (Thompson and Dinarello, 2009) relates to methods for improving the viability, recovery and functionality of islets that are separated from a donor organ for subsequent transplantation and more particularly relates to the use of eIF-5A1 siRNAs to enhance the viability and functionality of islets.
U.S. Patent Publication No. 20110008343 (Lambris et al. 2011) relates to methods for reducing rejection of pancreatic islet cells transplanted into a subject. The methods involve transplanting pancreatic islet cells into a subject in the presence of a complement inhibitor, alone or combined with dextran sulfate.